Review
Biochemistry & Molecular Biology
Yuzi You, Wei Liang
Summary: Aging is a complex biological process characterized by progressive functional deterioration and increased risk of mortality, driven by various mechanisms such as DNA damage, chronic inflammation, and metabolic dysfunction. Sirtuins (SIRTs), a family of NAD+-dependent enzymes, play important roles in regulating aging-related processes. Among the seven mammalian SIRT isotypes (SIRT1-7), SIRT1 and SIRT6 are well-known for their roles in regulating signaling pathways related to aging. This review discusses the protective effects of SIRT1 and SIRT6 in aging-related diseases at multiple levels and explores the therapeutic potential of SIRT1 and SIRT6 modulators in the treatment of these diseases and the challenges involved.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2023)
Article
Cell Biology
Lindsay E. Wu, Corrine E. Fiveash, Nicholas L. Bentley, Myung-Jin Kang, Hemna Govindaraju, Jayne A. Barbour, Brendan P. Wilkins, Sarah E. Hancock, Romanthi Madawala, Abhijit Das, Hassina Massudi, Catherine Li, Lynn-Jee Kim, Ashley S. A. Wong, Maria B. Marinova, Ghazal Sultani, Abhirup Das, Neil A. Youngson, David G. Le Couteur, David A. Sinclair, Nigel Turner
Summary: The NAD+-dependent deacylase family of sirtuin enzymes, including SIRT2, play important roles in biological aging, late-life health, and overall lifespan. However, the role of SIRT2 has been less clear. Previous studies showed that transgenic overexpression of SIRT2 can improve health and increase lifespan in a progeria model. In this study, the researchers tested whether SIRT2 overexpression would impact the overall health and lifespan of mice on a nonprogeroid, wild-type background. They found that SIRT2 overexpression did not have an additional impact on health or lifespan in these mice. Biochemical studies also revealed changes in brain metabolites in SIRT2 overexpressing mice, but these changes did not translate into functional differences.
Article
Multidisciplinary Sciences
Mahmoud A. A. Ibrahim, Khlood A. A. Abdeljawaad, Eslam Roshdy, Dina E. M. Mohamed, Taha F. S. Ali, Gamal A. Gabr, Laila A. Jaragh-Alhadad, Gamal A. H. Mekhemer, Ahmed M. Shawky, Peter A. Sidhom, Alaa H. M. Abdelrahman
Summary: In this study, potential SIRT2 inhibitors were identified from a natural product database using in silico techniques. Three compounds with better binding affinity towards SIRT2 protein were found and their drug-likeness and pharmacokinetic characteristics were predicted.
SCIENTIFIC REPORTS
(2023)
Article
Biochemistry & Molecular Biology
Teng Ai, Daniel J. Wilson, Liqiang Chen
Summary: This study explores SIRT2 inhibitors based on the 3-aminobenzyloxy nicotinamide scaffold and identifies 2,3-constrained (S)-isomers with enhanced enzymatic inhibitory activity against SIRT2 and excellent selectivity over SIRT1 and SIRT3. These findings contribute to the discovery of potent, selective SIRT2 inhibitors for potential therapeutic applications.
Article
Multidisciplinary Sciences
Shiv Bharadwaj, Amit Dubey, Nitin Kumar Kamboj, Amaresh Kumar Sahoo, Sang Gu Kang, Umesh Yadava
Summary: A computational screening of FDA-approved drugs identified 48 potential inhibitors of Sirt2, with Fluphenazine and Nintedanib showing substantial stability in Sirt2-drug complexes. The developed 3D-QSAR models supported the inhibitory potential of the drugs, highlighting Nintedanib as the most active compound with promising Sirt2 inhibition properties. Further in vitro investigation is required for drug development targeting Sirt2.
SCIENTIFIC REPORTS
(2021)
Review
Geriatrics & Gerontology
Wei Wan, Fuzhou Hua, Pu Fang, Chang Li, Fumou Deng, Shoulin Chen, Jun Ying, Xifeng Wang
Summary: Sirtuins are protein factors that can delay aging and alleviate age-related diseases through multiple pathways. They promote DNA damage repair, delay telomere shortening, and mediate mitochondrial quality control through mitophagy, preventing the accumulation of dysfunctional mitochondria.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Francisco Alejandro Lagunas-Rangel
Summary: Aging is caused by the accumulation of molecular and cellular damage over time. SIRT7, an enzyme with important functions in aging and life extension, has been found to be closely related to age-related processes and may be associated with certain age-related diseases.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Geriatrics & Gerontology
Robertina Giacconi, Leonardo Chiodi, Gianfranco Boccoli, Laura Costarelli, Francesco Piacenza, Mauro Provinciali, Marco Malavolta
Summary: The study revealed an independent association between selenium deficiency and cardiovascular disease, leading to elevated inflammatory markers and impacting the expression of cytokines, chemokines, and sirtuins in PBMCs.
EXPERIMENTAL GERONTOLOGY
(2021)
Article
Chemistry, Medicinal
Jian Yao, Yudong Yin, Hong Han, Shaoting Chen, Yuxiang Zheng, Benji Liang, Mengyue Wu, Kangqi Shu, Bikash Debnath, David B. Lombard, Quande Wang, Keguang Cheng, Nouri Neamati, Yanghan Liu
Summary: In this study, a novel SIRT5-selective inhibitor was identified and optimized, resulting in compound 47 with 100-fold improved potency. Compound 47 showed substantial selectivity for SIRT5 and acted as a substrate-competitive inhibitor. These findings provide possibilities for further research and development of therapeutic tools and drugs.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Pharmacology & Pharmacy
Yanhong Song, Ziyi Wu, Ping Zhao
Summary: Metformin is a widely used hypoglycemic agent with anti-aging effects. Aging-related diseases of the musculoskeletal system can significantly impact quality of life in the elderly. This review discusses the mechanisms by which metformin regulates aging in the musculoskeletal system, including its contributions to bone homeostasis, muscle aging, and joint degeneration. The protective benefits of metformin in aging-related diseases are also analyzed.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Naomi Scarano, Elena Abbotto, Francesca Musumeci, Annalisa Salis, Chiara Brullo, Paola Fossa, Silvia Schenone, Santina Bruzzone, Elena Cichero
Summary: This article focuses on the selective inhibitors of SIRT2 enzyme. By using SBVS method, a potential molecular scaffold for designing new SIRT2 inhibitors was identified. Experimental results showed that this molecular scaffold exhibited strong SIRT2 inhibitory activity, validating the effectiveness of the research strategy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biology
Danial Khayatan, Seyed Mehrad Razavi, Zahra Najafi Arab, Maryam Khanahmadi, Saeideh Momtaz, Alexandra E. Butler, Fabrizio Montecucco, Yuliya V. Markina, Amir Hossein Abdolghaffari, Amirhossein Sahebkar
Summary: This research summarizes the impact of statins on SIRT proteins and their correlation with cardiovascular diseases, providing a foundation for further investigation in this field.
Article
Biochemistry & Molecular Biology
Mingjie Gao, Aurelien F. A. Moumbock, Ammar Qaseem, Qianqing Xu, Stefan Guenther
Summary: CovPDB is the first database dedicated solely to high-resolution cocrystal structures of biologically relevant cP-L complexes, containing 733 proteins and 1,501 ligands relating to 2,294 cP-L complexes.
NUCLEIC ACIDS RESEARCH
(2022)
Review
Cell Biology
Caterina Miceli, Manuela Leri, Massimo Stefani, Monica Bucciantini
Summary: Autophagy plays a key role in maintaining cellular and organismal homeostasis, providing the necessary energy during critical development stages and nutrient shortage. It is considered a pro-survival mechanism, but its dysregulation is associated with non-apoptotic cell death. Declining autophagy efficiency with age contributes to various pathological conditions, including cancer, cardiomyopathy, diabetes, liver disease, autoimmune diseases, infections, and neurodegeneration. Understanding the relationship between autophagy and age-related pathologies is crucial for proposing disease prevention strategies and potential clinical applications for long-term health promotion.
AGEING RESEARCH REVIEWS
(2023)
Review
Cell Biology
Taku Kaitsuka, Masayuki Matsushita, Nobuko Matsushita
Summary: Members of the sirtuin family play crucial roles in aging, metabolism, stress responses, and aging-related diseases, with SIRT2 being a unique sirtuin expressed in the cytosol and abundant in neuronal cells. Recent studies have focused on the regulation of stress responses by SIRT2, posttranscriptional regulation of SIRT2 by microRNAs, and the implications of the SIRT2-miRNA axis in aging-related diseases.
Article
Multidisciplinary Sciences
Shinya Watanabe, Dongyan Tan, Mahadevan Lakshminarasimhan, Michael P. Washburn, Eun-Jin Erica Hong, Thomas Walz, Craig L. Peterson
NATURE COMMUNICATIONS
(2015)
Article
Biochemical Research Methods
Mahadevan Lakshminarasimhan, Gina Boanca, Charles A. S. Banks, Gaye L. Hattem, Ana E. Gabriel, Brad D. Groppe, Christine Smoyer, Kate E. Malanowski, Allison Peak, Laurence Florens, Michael P. Washburn
MOLECULAR & CELLULAR PROTEOMICS
(2016)
Article
Cell Biology
Mahadevan Lakshminarasimhan, David Rauh, Mike Schutkowski, Clemens Steegborn
Article
Biochemistry & Molecular Biology
Mahadevan Lakshminarasimhan, Marien T. Maldonado, Wenbo Zhou, Anthony L. Fink, Mark A. Wilson
Article
Biochemistry & Molecular Biology
Anna C. Witt, Mahadevan Lakshminarasimhan, Benjamin C. Remington, Sahar Hasim, Edwin Pozharski, Mark A. Wilson
Article
Biochemistry & Molecular Biology
Mahadevan Lakshminarasimhan, Ute Curth, Sebastien Moniot, Shyamal Mosalaganti, Stefan Raunser, Clemens Steegborn
BIOSCIENCE REPORTS
(2013)
Article
Geriatrics & Gerontology
Mahadevan Lakshminarasimhan, Clemens Steegborn
EXPERIMENTAL GERONTOLOGY
(2011)
Article
Biochemistry & Molecular Biology
Jeff Blackinton, Mahadevan Lakshminarasimhan, Kelly J. Thomas, Rili Ahmad, Elisa Greggio, Ashraf S. Raza, Mark R. Cookson, Mark A. Wilson
JOURNAL OF BIOLOGICAL CHEMISTRY
(2009)
Article
Biochemistry & Molecular Biology
Mahadevan Lakshminarasimhan, Peter Madzelan, Ruth Nan, Nicole M. Milkovic, Mark A. Wilson
JOURNAL OF BIOLOGICAL CHEMISTRY
(2010)
Article
Biochemical Research Methods
Charles A. S. Banks, Zachary T. Lee, Gina Boanca, Mahadevan Lakshminarasimhan, Brad D. Groppe, Zhihui Wen, Gaye L. Hattem, Chris W. Seidel, Laurence Florens, Michael P. Washburn
MOLECULAR & CELLULAR PROTEOMICS
(2014)
Article
Multidisciplinary Sciences
Frank Fischer, Melanie Gertz, Benjamin Suenkel, Mahadevan Lakshminarasimhan, Mike Schutkowski, Clemens Steegborn
Article
Multidisciplinary Sciences
Melanie Gertz, Frank Fischer, Giang Thi Tuyet Nguyen, Mahadevan Lakshminarasimhan, Mike Schutkowski, Michael Weyand, Clemens Steegborn
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2013)
Article
Multidisciplinary Sciences
David Rauh, Frank Fischer, Melanie Gertz, Mahadevan Lakshminarasimhan, Tim Bergbrede, Firouzeh Aladini, Christian Kambach, Christian F. W. Becker, Johannes Zerweck, Mike Schutkowski, Clemens Steegborn
NATURE COMMUNICATIONS
(2013)
Article
Biochemistry & Molecular Biology
A Bérczi, D Su, M Lakshminarasimhan, A Vargas, H Asard
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2005)